The influence of scar on the spatio-temporal relationship between electrical and mechanical activation in heart failure patients.

AIMS: The aim of this study was to determine the relationship between electrical and mechanical activation in heart failure (HF) patients and whether electromechanical coupling is affected by scar. METHODS AND RESULTS: Seventy HF patients referred for cardiac resynchronization therapy or biological therapy underwent endocardial anatomo-electromechanical mapping (AEMM) and delayed-enhancement magnetic resonance (CMR) scans. Area strain and activation times were derived from AEMM data, allowing to correlate mechanical and electrical activation in time and space with unprecedented accuracy. Special attention was paid to the effect of presence of CMR-evidenced scar. Patients were divided into a scar (n = 43) and a non-scar group (n-27). Correlation between time of electrical and mechanical activation was stronger in the non-scar compared to the scar group [R = 0.84 (0.72-0.89) vs. 0.74 (0.52-0.88), respectively; P = 0.01]. The overlap between latest electrical and mechanical activation areas was larger in the absence than in presence of scar [72% (54-81) vs. 56% (36-73), respectively; P = 0.02], with smaller distance between the centroids of the two regions [10.7 (4.9-17.4) vs. 20.3 (6.9-29.4) % of left ventricular radius, P = 0.02]. CONCLUSION: Scar decreases the association between electrical and mechanical activation, even when scar is remote from late activated regions.

Stereotactic management of arrhythmia - radiosurgery in treatment of ventricular tachycardia (SMART-VT). Results of a prospective safety trial.

BACKGROUND AND PURPOSE: Despite its increasing popularity, there are limited prospective data on stereotactic arrhythmia radioablation (STAR). In this trial, we assessed the safety and efficacy of STAR in patients with ventricular tachycardia (VT), focusing on early treatment-related grade ≥ 3 adverse events (AE). MATERIALS AND METHODS: This prospective trial was designed for adults with VT recurrence following catheter ablation (CA) despite adequate pharmacotherapy, or contraindications to CA. A single dose of 25 Gy was delivered to the arrhythmia substrate defined on electro-anatomic mapping and cardiac-gated CT. The primary endpoint was safety, defined as two or fewer treatment-related grade ≥ 3 AEs during the first three months in 11 patients. Additional endpoints included treatment efficacy, clinical and biological markers of cardiac injury, and quality of life. RESULTS: Eleven patients with a median age of 67 years, structural heart disease, and a clinically significant recurrence of VT despite adequate pharmacotherapy and 1-4 previous CAs were enrolled between 2020/09 and 2022/10. Following the treatment, one patient developed a possibly treatment-related grade ≥ 3 AE, a grade 4 heart failure exacerbation at 87 days, which resolved after conservative treatment. There was a total 84.3% reduction in VT burden in 10 evaluable patients; however, VT recurrence was eventually observed in eight, and three patients required additional CAs. Three deaths due to unrelated causes were recorded. CONCLUSIONS: STAR appears to be safe and efficient. It is a promising treatment for selected patients; however, long-term outcomes remain to be evaluated, and controlled trials comparing STAR with standards of care are missing.

Radiosurgery in Treatment of Ventricular Tachycardia - Initial Experience Within the Polish SMART-VT Trial.

Background: Stereotactic Arrhythmia Radioablation (STAR) is an emerging treatment modality for patients with sustained ventricular tachycardia (VT) and refractory to treatment with drugs and radiofrequency catheter ablation (RFA). It is believed that up to 12-17% of patients experience recurrence of VT within 1 year of follow-up; thus, novel therapeutic options are needed. The aim of this article is to present initial experience within a novel treatment modality for VT. Case Summary: Two patients with a medical history of coronary artery disease and heart failure with reduced left ventricle (LV) ejection fraction, after implantation of cardioverter-defibrillator (ICD) and previous unsuccessful RFAs owing to sustained VT were admitted to the cardiology department due to recurrence of sustained VT episodes. With electroanatomical mapping (EAM), the VT substrate in LV has been confirmed and specified. In order to determine the target volume for radioablation, contrast-enhanced computed tomography was performed and the arrhythmia substrate was contoured using EAM data. Using the Volumetric Modulated Arc Therapy technique and three 6 MeV flattening filter-free photon beam fields, a single dose of 25 Gy was delivered to the target volume structure located in the apex and anterior apical segments of LV in the first patient and in the apex, anterolateral and inferior apical segments of the second patient. In both cases, volumes of the target structures were comparable. Interrogation of the implanted ICD at follow-up visits throughout 6 months after the treatment revealed no VT episodes in the first patient and sudden periprocedural increase in VT burden with a subsequent gradual decrease of ventricular arrhythmia to only two non-sustained episodes at the end of the follow-up period in case of the second patient. A significant reduction in premature ventricular contractions burden was observed compared to the pre-treatment period. No noticeable deterioration in LV function was noted, nor any adverse effects of radiosurgery associated with the implanted device. Conclusion: The early response to STAR can be unpredictable and probably does not reflect the final outcome of irradiation. Close monitoring of patients, especially in the early period after irradiation is crucial to properly handle potentially harmful early reactions to STAR.

Histopathological Examination of an Explanted Heart in a Long-Term Responder to Cardiac Stereotactic Body Radiotherapy (STereotactic Arrhythmia Radioablation).

Cardiac stereotactic body radiotherapy is an emerging treatment method for recurrent ventricular tachycardia refractory to invasive treatment methods. The single-fraction delivery of 25 Gy was assumed to produce fibrosis, similar to a post-radiofrequency ablation scar. However, the dynamics of clinical response and recent preclinical findings suggest a possible different mechanism. The data on histopathological presentation of post-radiotherapy hearts is scarce, and the authors provide significantly different conclusions. In this article, we present unique data on histopathological examination of a heart explanted from a patient who had a persistent anti-arrhythmic response that lasted almost a year, until a heart failure exacerbation caused a necessity of a heart transplant. Despite a complete treatment response, there was no homogenous transmural fibrosis in the irradiated region, and the overall presentation of the heart was similar to other transplanted hearts of patients with advanced heart failure. In conclusion, our findings support the theorem of functional changes as a source of the anti-arrhythmic mechanism of radiotherapy and show that durable treatment response can be achieved in absence of transmural fibrosis of the irradiated myocardium.

Correlation between electromechanical parameters (NOGA XP) and changes of myocardial ischemia in patients with refractory angina.

INTRODUCTION: Cell therapy has the potential to improve symptoms and clinical outcomes in refractory angina (RFA). Further analyses are needed to evaluate factors influencing its therapeutic effectiveness. AIM: Assessment of electromechanical (EM) parameters of the left ventricle (LV) and investigation of correlation between EM parameters of the myocardium and response to CD133+ cell therapy. MATERIAL AND METHODS: Thirty patients with RFA (16 active and 14 placebo individuals) enrolled in the REGENT-VSEL trial underwent EM evaluation of the LV with intracardiac mapping system. The following parameters were analyzed: unipolar voltage (UV), bipolar voltage (BV), local linear shortening (LLS). Myocardial ischemia was evaluated with single-photon emission computed tomography (SPECT). The median value of each EM parameter was used for intra-group comparisons. RESULTS: Global EM parameters (UV, BV, LLS) of LV in active and placebo groups were 11.28 mV, 3.58 mV, 11.12%, respectively; 13.00 mV, 3.81 mV, 11.32%, respectively. EM characteristics analyzed at global and segmental levels did not predict response to CD133+ cell therapy in patients with RFA (Global UV, BV and LLS at rest R = -0.06; R = 0.2; R = -0.1 and at stress: R = 0.07, R = 0.09, R = -0.1, respectively; Segmental UV, BV, LLS at rest R = -0.2, R = 0.03, R = -0.4 and at stress R = 0.02, R = 0.2, R = -0.2, respectively). Multiple linear regression of the treated segments showed that only pre-injection SPECT levels were significantly correlated with post-injection SPECT, either at rest or stress (p < 0.05). CONCLUSIONS: Electromechanical characteristics of the left ventricle do not predict changes of myocardial perfusion by SPECT after cell therapy. Baseline SPECT results are only predictors of changes of myocardial ischemia observed at 4-month follow-up.

Local electromechanical alterations determine the left ventricle rotational dynamics in CRT-eligible heart failure patients.

Left ventricle, LV wringing wall motion relies on physiological muscle fiber orientation, fibrotic status, and electromechanics (EM). The loss of proper EM activation can lead to rigid-body-type (RBT) LV rotation, which is associated with advanced heart failure (HF) and challenges in resynchronization. To describe the EM coupling and scar tissue burden with respect to rotational patterns observed on the LV in patients with ischemic heart failure with reduced ejection fraction (HFrEF) left bundle branch block (LBBB). Thirty patients with HFrEF/LBBB underwent EM analysis of the left ventricle using an invasive electro-mechanical catheter mapping system (NOGA XP, Biosense Webster). The following parameters were evaluated: rotation angle; rotation velocity; unipolar/bipolar voltage; local activation time, LAT; local electro-mechanical delay, LEMD; total electro-mechanical delay, TEMD. Patients underwent late-gadolinium enhancement cMRI when possible. The different LV rotation pattern served as sole parameter for patients' grouping into two categories: wringing rotation (Group A, n = 6) and RBT rotation (Group B, n = 24). All parameters were aggregated into a nine segment, three sector and whole LV models, and compared at multiple scales. Segmental statistical analysis in Group B revealed significant inhomogeneities, across the LV, regarding voltage level, scar burdening, and LEMD changes: correlation analysis showed correspondently a loss of synchronization between electrical (LAT) and mechanical activation (TEMD). On contrary, Group A (relatively low number of patients) did not present significant differences in LEMD across LV segments, therefore electrical (LAT) and mechanical (TEMD) activation were well synchronized. Fibrosis burden was in general associated with areas of low voltage. The rotational behavior of LV in HF/LBBB patients is determined by the local alteration of EM coupling. These findings serve as a strong basic groundwork for a hypothesis that EM analysis may predict CRT response.Clinical trial registration: SUM No. KNW/0022/KB1/17/15.

Multimodality intravascular imaging of bioresorbable vascular scaffolds implanted in vein grafts.

INTRODUCTION: There are no data presenting a serial assessment of vein graft healing after bioresorbable vascular scaffold (BVS) implantation at long-term follow-up. AIM: To describe ABSORB BVS healing in vein grafts by optical coherence tomography (OCT) and high-definition intravascular imaging (HD-IVUS) at long-term follow-up.Material and methods: The study group consisted of 6 patients. The first patient had serial OCT assessment of BVS implanted in the saphenous vein grafts (SVG) at baseline and at 3-, 6-, 18-month follow-up and the second patient had OCT assessment of BVS implanted in the SVG at baseline and 24-, 48-month follow-up. The second and the third patients had OCT and HD-IVUS imaging at baseline and 48-month follow-up. The last 3 patients had OCT imaging of BVS implanted in the native coronary artery at 48-month follow-up. RESULTS: There were no differences in neointimal hyperplasia after BVS implantation between each time point. However, complete scaffold coverage was observed only 48 months after implantation. Out of 202 analyzed scaffold struts, there were 67 (33%) black boxes detectable at 48-month follow-up. HD-IVUS presented plaque burden up to 67% at the segment of BVS implantation at 48-months follow-up. There was a difference in neointimal hyperplasia thickness (1.27 (0.953-1.696) vs. 0.757 (0.633-0.848), p < 0.001) between a native coronary artery and BVS scaffolds at 48-month follow-up. CONCLUSIONS: Bioresorbable vascular scaffold implanted in SVG characterized moderate neointimal hyperplasia as excessive as compared to native coronary arteries at long-term follow-up. The complete scaffold coverage was observed only 48 months after implantation.

Serum Concentrations of Osteogenesis/Osteolysis-Related Factors and Micro-RNA Expression in ST-Elevation Myocardial Infarction.

BACKGROUND: Atherosclerosis and bone metabolism share similar molecular and cellular mechanisms. This study aims to evaluate (1) serum concentration of osteogenesis/osteolysis factors panel (Dickkopf-related protein 1 (DKK-1), TNF-α, N-terminal atrial natriuretic peptide (NT-proANP), thrombospondin-2 (TSP-2), osteoprotegerin (OPG), osteocalcin (OCN), osteopontin (OPN), fibroblast growth factor 23 (FGF-23), soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), proprotein convertase subtilisin/kexin type 9 (PCSK9)), (2) serum expression levels of micro-RNA- (miR-) 24-1 and miR-6802, and (3) assess their correlation with myocardial injury and LV remodeling and function in the acute phase of STEMI and after 3 months. METHODS: Study enrolled 25 STEMI patients (mean age 55.4 ± 8.96 years). Blood samples were collected 4 days and 3 months after myocardial infarction. Serum concentrations of osteogenesis/osteolysis factors were measured using the Luminex assay. Analysis of miR-24-1, and miR-6802 expression was performed with qPCR. LV function and remodeling were assessed by MRI during index hospitalization and 3 months later. RESULTS: There were no significant differences in serum levels of osteogenesis/osteolysis factors and expression of miR-24-1 and miR-6802 between the acute phase and 3-month follow-up. The levels were similar in patients with at least ≥5% improvement of LVEF (n = 10) and those without improvement. There was a negative correlation between the OPG serum level and LVEF during the acute phase of myocardial infarction. CONCLUSIONS: In STEMI patients, serum concentrations of osteogenesis/osteolysis factors, as well as miR-24-1 and miR-6802 expression, do not change significantly within the 3-month follow-up and are not correlated with LV remodeling and function.